Esters of bi- and tricyclic amino alcohols, their preparation and their use in pharmaceutical compositions

ABSTRACT

The new compounds of formula 
     
         A--O--CO--Z                                                (I) 
    
     (wherein A and Z are defined as explained in the specification) can be prepared by conventional methods; they are suitable as active substances for pharmaceutical compositions.

This is a continuation of application Ser. No. 08/117,199, filed Dec. 2,1993, abandoned.

The invention relates to new esters of bi- and tricyclic amino alcohols,the preparation of these compounds and their use in pharmaceuticalcompositions.

The new compounds correspond to the formula

    A--O--CO--Z                                                (I)

wherein

A represents the group ##STR1## wherein m represents 0, 1 or 2,

n represents 1 or 2 and m+n<3,

Q represents one of the double-bonded groups --CH₂ --CH₂ --, --CH₂ --CH₂--CH₂ --, --CH═CH--, ##STR2## or --CH₂ --Q"--(CH₂)_(p) --(p=0 or 1) and

Q' represents the group ═NR, the group ═NRR' or the group CH₂, wherein Rrepresents an optionally halo- or hydroxy-substituted C₁₋₄ -alkyl group,R' represents a C₁₋₄ -alkyl group and R and R' together may also form aC₄₋₆ -alkylene group, and, in the case of quaternary compounds, anequivalent of an anion (X.sup.θ), is associated with the positive chargeof the N-atom, and

Q" has the same meanings as Q', with the exception of CH₂, and with theproviso that Q represents --CH₂ --Q"--(CH₂)_(p) -- when Q' representsCH₂,

Z represents the group ##STR3## wherein R₁ represents H, OH, CH₂ OH,C₁₋₄ -alkyl or C₁₋₄ -alkoxy,

R₂ and R₃, which may be identical or different and one of which may alsobe H, represent

(a) phenyl, furyl, an aromatic group which is isoelectronic withthienyl, C₅₋₇ -cycloalkyl, pyridyl, C₅₋₇ -cycloalkenyl or, in particularif m is equal to O and/or Q is equal to --CH₂ --Q"--(CH₂)_(p), R₂, mayalso represent thienyl,

(b) an aliphatic group having up to 20 carbon atoms optionallyinterrupted by oxygen, or a C₁₋₆ -alkyl group substituted by phenyl,phenoxy, thienyl, furyl, C₅₋₇ -cycloalkyl or fluorine,

(c) the entire group III may also represent the tricyclic group of theformula ##STR4## or a group of formula ##STR5## wherein B may representS or CH═CH, R'₁ has the same meaning as R₁ and may additionallyrepresent phenyl, thienyl, furyl, thiazolyl, thiadiazolyl ormethoxyphenyl, Y represents a single bond, an O- or S-atom or one of thegroups --CH₂ --, --CH₂ --CH₂ --, --CH═CH--, --OCH₂ -- or --S--CH₂ -- andq represents 1, 2 or 3.

In the compounds of formula I R₂ preferably represents OH. The group--OA preferably has an α-configuration and is derived for example fromscopine, tropine, granatoline or 6,7-dehydrotropine or the correspondingnor-compounds; --OA may, however, also have the β-configuration as inpseudotropine or pseudoscopine.

Examples of corresponding groups include: ##STR6##

The substituent R is preferably a lower alkyl group, especially CH₃, ormay also represent, for example, C₂ H₅, n-C₃ H₇, i-C₃ H₇ and R'preferably represents CH₃. R and R' together may represent, for example,--(CH₂)₅ --. The halogen substituent for R is preferably F or, to alesser extent, Cl. If R represents a halo- or hydroxy-substituted alkylgroup it is preferably --CH₂ --CH₂ F or --CH₂ --CH₂ OH. Accordingly, thegroup A represents, for example, the groups of scopine,N-ethylnorscopine, N-isopropylnorscopine, tropine,N-isopropylnortropine, 6,7-dehydrotropine, N-β-fluoroethylnortropine,N-isopropyl-6,7-dehydronortropine, N-methylgranatoline or thecorresponding quaternary compounds, the anion preferably being Br.sup.θor CH₃ So₃.sup.θ.

The group Z may have the following meanings, for example, whilst thearomatic groups may also be substituted, e.g. by CH₃, OCH₃, F or Cl:##STR7##

If in the group II m represents O and/or Q represents --CH₂--Q"--(CH₂)_(p) --, the group III may have the following additionalmeanings, in particular: ##STR8##

The quaternary compounds of formula I are particularly suitable fortherapeutic use, while the tertiary compounds are important not only asactive substances but also as intermediate products.

The compounds according to the invention are anticholinergics with apotent and long-lasting effect. At dosages in the microgram range,periods of effect of more than 24 hours are achieved after inhalation.Moreover, the toxicity is in the same range as that of the standardcommercial product ipratropium bromide, whilst at the same time thetherapeutic effect is in some cases significantly greater.

In accordance with their nature as anticholinergics, the new compoundsare suitable, for example, for treating chronically obstructivebronchitis and (slight to moderate) asthma and also for treating vagallyinduced sinus bradycardia. Whereas in diseases of the respiratory tractit is chiefly recommended to administer the new active substances byinhalation (especially the quaternary compounds), thereby largelyeliminating any side effects, the compounds are preferably administeredby intravenous or oral route in the case of sinus bradycardia. It hasbeen found to be advantageous that the new compounds have virtually noeffect on gastrointestinal motility.

For use, the compounds according to the invention are processed withknown excipients and/or carriers to form conventional galenicpreparations, e.g. solutions for inhalation, suspensions in liquefiedpropellant gases, preparations containing liposomes or proliposomes,injectable solutions, plain or coated tablets, capsules, powders forinhalation for use in conventional inhalers.

Examples of formulations (amounts given in percent by weight):

1Metering aerosol

    ______________________________________                                        Active substance according to                                                                          0.005                                                the invention                                                                 Sorbitantrioleate        0.1                                                  Monofluorotrichloromethane and                                                                         to 100                                               difluorodichloromethane 2:3                                                   ______________________________________                                    

The suspension is poured into a conventional aerosol container with ametering valve.

Preferably, 50 μl of suspension are dispensed on each actuation. Theactive substance may also be dispensed in a higher dosage if desired(e.g. 0.02% by weight).

2. Tablets

    ______________________________________                                        Active substance according to                                                                     0.05                                                      the invention                                                                 Colloidal silica    0.95                                                      Lactose             65.00                                                     Potato starch       28.00                                                     Polyvinylpyrrolidone                                                                              3.00                                                      Na-cellulose glycolate                                                                            2.00                                                      Magnesium stearate  1.00                                                      ______________________________________                                    

The ingredients are processed in the usual way to form tablets weighing200 mg.

The advantageous properties of the new compounds are found for examplein their inhibition of broncholysis in rabbits (acetylcholine spasmi.v.). After intravenous administration of the new active substances(dosage 3 μg/kg i.v.) the maximum effect was obtained after 10 to 40minutes. Even on isolated organs, e.g. on the guinea-pig ileum orrectum, numerous compounds according to the invention were found to havea long duration of activity.

The new compounds may be prepared by methods known per se.

1. Preferably an ester of formula

    Z--CO--OR"                                                 (VII),

wherein Z is as hereinbefore defined and R" represents a C₁₋₄ -alkylgroup, preferably methyl or ethyl, is transesterified, in the presenceof a conventional transesterification catalyst, with an aminoalcohol offormula ##STR9## wherein m and n are as hereinbefore defined, Q'_(a)represents NR' or NH, Q_(a) has the same meaning as Q, with the provisothat if Q_(a) represents --CH₂ --Q"--(CH₂)_(p) --, Q" can only representNR', and wherein the OH-group is in the α- or β-position, or

2. a reactive derivative (R'" represents a readily cleavable group)

    Z--CO--OR"'                                                (IX)

of the acid Z--CO--OH, particularly an acid chloride or imidazolidethereof, is reacted with an alcohol of formula VIII, optionally inexcess or in the presence of a tertiary amine such as triethylamine, andoptionally the resulting compound

a) if Q'_(a) represents NR', is quaternised with a reactivemonoderivative X--R of a corresponding alkane (X=leaving group) or

b) if Q' _(a) represents NH, is quaternised with a terminallydisubstituted alkane X--(C₄₋₆ -9alkylene)--X without intermediateisolation or

c) if Q_(a) equals --CH₂ --NR'--(CH₂)_(p) --, is quaternised with areactive monoderivative X--R.

Alternatively, starting compounds may be quaternised, in which thestarting compound VIII contains R representing a "halo- orhydroxy-substituted alkyl group" instead of R' at the nitrogen atom.

The transesterification according to process 1 is carried out withheating in an organic solvent, e.g. toluene, xylene or heptane, or in amelt, using strong bases such as sodium methoxide, sodium ethoxide,sodium hydride or metallic sodium as catalyst. In order to eliminate thelower alcohol released from the equilibrium, reduced pressure is used,and possibly the alcohol is distilled off azeotropically. Thetransesterification is carried out at temperatures generally notexceeding 95° C. Frequently, trans-esterification proceeds more easilyin a melt. The reaction according to process 2 is carried out in anorganic solvent or mixture of solvents which is sufficiently inert underthe reaction conditions, e.g. acetone or acetonitrile, at temperaturesbetween about 0° C. and the boiling temperature of the reaction mixture.

The free bases may be obtained from acid addition salts of the tertiaryamines, if desired, using suitable basic compounds in a manner known perse. The quaternisation is carried out in suitable solvents, e.g.acetonitrile or acetonitrile/methylene chloride, preferably at ambienttemperature; the preferred quaternising reagent is a corresponding alkylhalide, e.g. alkyl bromide, or a corresponding sulphonic acidderivative, e.g. a methane- or toluenesulphonic acid derivative.Transesterification products wherein Q' represents NH are used asstarting materials for those compounds in which R and R' togetherrepresent a C₄₋₆ -alkylene group. Conversion into the tertiary and thenquaternary compound is carried out using suitable 1,4-, 1,5- or1,6-dihaloalkanes without intermediate isolation.

The starting compounds, where they have not already been described, maybe obtained analogously to known compounds.

EXAMPLES

Methyl di-(2-thienyl)glycolate from dimethyloxalate and2-thienylmagnesium bromide;

Ethyl di-(2-thienyl)glycolate from (2-thienyl)glyoxylic: acid and2-thienyllithium;

Ethyl hydroxyphenyl-(2-thienyl)acetate from methylphenylglyoxylate and2-thienylmagnesium bromide or from methyl (2-thienyl)glyoxylate andphenylmagnesium bromide.

Similarly, methyl 2-thienylglyoxylate and cyclohexyl- orcyclopentylmagnesium bromide may be reacted.

There are also several possible methods of preparing the aminoalcohols.

Pseudoscopine can be obtained according to M. Polonovski et al., Bull.soc. chim. 43, 79 (1928).

Pseudotropenol can be isolated from the mixture (by fractionalcrystallisation or distillation) which is obtained, for example,according to V. Hayakawa et al., J. Amer.Chem.Soc. 1978, 100(6), 1786 orR. Noyori et al., J.Amer.Chem.Soc. 1974, 96(10), 3336.

N-ethylnorscopine and N-isopropylnorscopine may be prepared byhydrogenolysis from the corresponding N-alkylnorscopolamines analogouslyto Banholzer DE-A P 3215933. 6-methyl-6-azabicyclo 3.2.1!octan-3-α-olcan be prepared according to F. I. Carroff et al., J. Med.Chem. 30, 805(1987), and 7-methyl-7-azabicyclo- 2.2.1!heptan-2α-ol may be obtainedaccording to J. R. Pfister et al., J. Pharmac. Sciences 74, 208 (1985).

Starting from 2- or 3-furylglyoxylnitrile the corresponding methylestersmay be prepared in conventional manner via the 2- or 3-furylglyoxylicacid obtainable from the starting material. From these methylesters, thecorresponding glycolic acid esters may be obtained as described with theorganometallic derivatives of 2- or 3-bromothiophene. The organometalliccompounds obtainable from 2-, 3- or 4-halopyridine can be reacted withmethyl 2- or 3-thienylglyoxylate to obtain the corresponding glycolicacid esters.

Thienylglycolic acid esters in which the thiophene ring in the 2- or3-position contains fluorine may be obtained, for example, starting from2-fluorothiophene or 3-fluorothiophene (bromination to obtain 2-bromo-3-fluoro- or 2-bromo-5-fluorothiophene and, after conversion intocorresponding organometallic compounds, reaction with suitable glyoxylicacid esters to obtain the glycolic acid esters.

2-fluorothiophene and 3-fluorothiophene may be reacted analogously toUnterhalt, Arch.Pharm. 322, 839 (1989) to obtain the correspondingglyoxylic acid esters which may then in turn be reacted with 2- or3-thienyl derivatives, for example, to obtain glycolic acid esters, asdescribed above. By a suitable choice of components, symmetricallysubstituted dithienylglycolic acid esters may be prepared analogously.

A method analogous to benzoin condensation and benzylic acidrearrangement is also possible.

The acid chlorides required may be obtained from the acids and thionylchloride whilst the imidazolides may be obtained from the acids andcarbonyldiimidazole.

The following Examples illustrate the invention without restricting it.

EXAMPLE 1

Benzylic acid scopine ester-methobromide

a) Benzylic acid scopine ester from α-chlorodiphenyl-acetic acidchloride and scopine

26.5 g (0.1 mol) α-chlorodiphenylacetic acid chloride are added to asolution of 31.0 g (0.2 mol) of scopine in 60 ml of anhydrous pyridineat 0° C. within 50 minutes with stirring. After it has all been addedthe mixture is stirred for 4 hours without cooling and then left tostand for 24 hours. In order to work up the mixture the scopinehydrochloride precipitated is suction filtered. The solution separatedoff is evaporated down under reduced pressure, the residue is dissolvedin a mixture of 600 ml of water and 15 ml of conc. hydrochloric acid andheated to about 80° C. for 10 minutes. At a temperature below 20° C.,sodium carbonate is added until a pH of 9 is achieved. The benzylic acidscopine ester is extracted with methylene chloride and the extracts aredried over sodium sulphate. After evaporation and treatment withacetone, white crystals are obtained, m.p. 182°-3° C. (decomp.), yield31.8 g (87% of theory). Elementary analysis and spectra confirm that thetitle compound has been obtained which can be converted in the usual wayinto the hydrochloride, m.p. 256° C. (decomp.; from ethanol).

b) Benzylic acid scopine ester from benzylic acid imidazolide andscopine

A suspension of 7.13 g (0.046 mol) of scopine and 3.2 g (0.0115 mol) ofbenzylic acid imidazolide in 50 ml of acetone is heated to boilingpoint. After about 10 minutes a further 9.6 g (0.0345 mol) of benzylicacid imidazolide are gradually added thereto. After the reaction hasended the mixture is cooled with ice/common salt. The crystalsprecipitated are suction filtered. They may be converted into thehydrochloride, m.p. 256° C. (decomp.; from ethanol). Yield 8.9 g, 53% oftheory).

c) Benzylic acid scopine,ester methobromide

7.12 g (0.075 mol) of methylbromide dissolved in acetone are added to asuspension of 5.48 g (0.015 mol) of benzylic acid scopine ester in 120ml of acetonitrile and 20 ml of carbon tetrachloride and the mixture isleft to stand under a slight overpressure until the reaction has ended.The crystals precipitated are suction filtered, washed with coldacetonitrile then with diethylether and after drying (at 40° C. underreduced pressure) recrystallised from methanol/ether, m.p. 200° C.(decomp.). Elementary analysis and spectrum confirm that the desiredcompound has been obtained.

EXAMPLE 2

1-N-β-Fluoroethylnorscopolamine-methobromide

a) 1-N-β-Fluoroethylnorscopolamine-hydrochloride

A mixture of 16.3 (0.05 mol) of 1-norscopolamine-hydrochloride, 6.3 g(0.05 mol) of 2-bromofluoroethane, 10.6 g (0.1 mol) of sodium carbonateand 100 ml of acetonitrile is refluxed for 6 hours. Then a further 6.3 g(0.05 mol) of 2-bromofluoroethane and 5.3 g (0.05 mol) of sodiumcarbonate are added and the mixture is heated for a further 24 hours.Finally, 3.2 g (0.025 mol) of 2-bromofluoroethane and 2.7 g (0.025 mol)of sodium carbonate are added and the mixture is heated for a further 48hours. It is suction filtered and the solution is concentrated byevaporation. The residue is taken up in methylene chloride, extractedwith water and the methylene chloride phase is dried over sodiumsulphate. After distillation of the methylene chloride an oily residueis obtained which is reacted in the usual way to form the hydrochloride.From methanol/ether 13.1 g of white crystals are obtained (70.4% oftheory), m.p. 197°-8° C. (decomp.).

b) Reaction to form the methobromide

7.0 g (0.021 mol) of the amine liberated in the usual way from thehydrochloride obtained in a) are reacted in 20 ml of absoluteacetonitrile with 9.9 g (0.104 mol) of methylbromide for 6 days under aslight overpressure. The crystals precipitated are recrystallised frommethanol/ether. 3.9 g of white crystals, m.p. 194° C. (decomp.).Elementary analysis and spectra confirm that the title compound has beenobtained.

EXAMPLE 3

Mandelic acid scopine ester methobromide

155.2 g (1.0 mol) of scopine are dissolved in 200 ml of absolutemethylene chloride and 116.9 g (0.55 mol) of acetylmandelic acidchloride dissolved in 100 ml of absolute methylene chloride are addeddropwise thereto (at 20° C. within 1 hour). (The acetylmandelic acidchloride is obtained from acetylmandelic acid and thionyl chloride).After one hour the scopine hydrochloride precipitated is separated off,the methylene chloride solution is extracted with water and dried.

The combined aqueous phases are made alkaline with sodium carbonate,extracted with methylene chloride and the methylene chloride phase isdried. The solvent is distilled off from the combined methylene chloridesolutions. The base which remains is converted into the hydrochloride inthe usual way. After recrystallisation from acetonitrile, 124.6 g (67.7%of theory) of white crystals are obtained, m.p. 207° C. (decomp.).

27.5 g (0.075 mol) of the acetyl compound thus obtained are left tostand in 110 ml of 20% hydrochloric acid for 20 hours at ambienttemperature. Whilst cooling, the reaction solution is made alkaline andthe mandelic acid scopine ester is extracted with methylene chloride.After drying over sodium sulphate and distillation of the solvent, thehydrochloride is prepared in the usual way. From methanol/ether, 22.5 g(92.4% of theory) of white crystals are obtained, m.p. 141°-2° C.

10.7 g (0.037 mol) of the ester liberated from the hydrochloride in theusual way are left to stand for 40 hours in acetonitrile with 17.58 g(0.185 mol) of methylbromide under a slight overpressure.

The crystals precipitated are suction filtered, washed with coldacetonitrile and recrystallised from methanol/ether. 10.0 g (70.4% oftheory) of white crystals are obtained, m.p. 223° C. (decomp.).

Elementary analysis and spectra confirm that the title compound has beenobtained.

EXAMPLE 4

Xanthene-9-carboxylic acid scopine ester methobromide

a) At 20° C., a solution of 11.1 g (0.11 mol) of triethylamine in 20 mlof acetone and 26.9 g (0.11 mol) of xanthene-9-carboxylic acid chloride(obtained from xanthene-9-carboxylic acid and thionyl chloride) in 80 mlof acetone are simultaneously added dropwise to a solution of 15.5 g(0.01 mol) of scopine in 50 ml of acetone at 20° C. After 4 hours afurther 1.1 g (0.01 mol) of triethylamine and 2.69 (0.011 mol) ofxanthene-9-carboxylic acid chloride are added. After 4 days the mixtureis suction filtered and the solvent is distilled off from the solution.Sodium carbonate solution is added to the residue and extracted withmethylene chloride. The organic phase is dried over sodium sulphate andthe solvent is distilled off. From the residue, the hydrochloride of theresulting xanthene-9-carboxylic acid scopine ester is obtained in theconventional manner; white crystals from acetonitrile/ether, m.p. 223°C. (decomp.); yield 21.8 g.

b) The base is liberated in the usual way from a sufficient quantity ofthe hydrochloride obtained in a). 36.3 g (0.1 mol) thereof are reactedin a solution of 47.5 g (0.5 mol) of methylbromide in 49 g ofacetonitrile for 24 hours under slight overpressure. The crystalsobtained are suction filtered, washed with acetone/ether andrecrystallised from ethanol. Yield 44.0 g (95.8% of theory), whitecrystals, m.p. 139° C. The crystals contain 0.5 mol of ethanol.Elementary analysis and spectra confirm the presence of the titlecompound.

The other compounds according to the invention may also be obtained inaccordance with the Examples given above. The compounds melt withdecomposition.

                  TABLE 1                                                         ______________________________________                                        Compounds of formula                                                           ##STR10##                                                                    No.   R.sub.1 A                     M.p.  °C.!                         ______________________________________                                        1     OH      3α-Tropanyl-methobromide                                                                      275-6                                     2     OH      3α-Tropanyl-β-fluorethobromide                                                           205-6                                     3     H       3α-N-Ethyl-(6β,7β-Epoxy)-                                                           228                                                     nortropanyl-methobromide                                        4     H       3α-N-Propyl-(6β,7β-Epoxy)-                                                          206-7                                                   nortropanyl-methobromide                                        5     H       3α-N-Isopropyl-(6β,7β-Epoxy)-                                                       218                                                     nortropanyl-methobromide                                        6     H       3α-(6β,7β-Epoxy)-                                                                   207                                                     tropanyl-methobromide                                           7     H       3α-(6,7-Dehydro)tropanyl-                                                                     226-8                                                   methobromide                                                    8     H       3α-Tropanyl-methobromide                                                                      275-6                                     9     H       3α-N-Ethyl-nortropanyl-methobromide                                                           256-7                                     10    H       (-)-3α-N-Isopropylnortropanyl-                                                                256                                                     methobromide                                                    11    H       (+)-3α-N-Isopropylnortropanyl-                                                                256                                                     methobromide                                                    12    H       3α-Nortropanyl-8,1'-                                                                          267-70                                                  pyrrolidinium-bromide                                           13    H       (+)-3α-Tropanyl-methobromide                                                                  278-81                                    14    H       (-)-3α-Tropanyl-methobromide                                                                  278-81                                    ______________________________________                                    

                  TABLE II                                                        ______________________________________                                        Compounds of formula                                                           ##STR11##                                                                    No.     R.sub.1 A                  M.p.  °C.!                          ______________________________________                                        1       OH      3α-N-Isopropylnortropanyl-                                                                 258                                                        methobromide                                                  2       OH      3α-N-β-Chlorethylnortropanyl-                                                         203                                                        methobromide                                                  3       OH      3α-N-Ethylnortropanyl-                                                                     269                                                        methobromide                                                  4       OH      3α-Tropanyl-ethobromide                                                                    258                                        5       OH      3α-(6β,7β-Epoxy)tropanyl-                                                        200                                                        methobromide                                                  6       OH      3α-N-Ethyl-(6β,7β-Epoxy)-                                                        220-1                                                      nortropanyl-methobromide                                      7       OH      3α-(6β,7β-Epoxy)-N-isopropyl-                                                    234-5                                                      nortropanyl-methobromide                                      8       OH      3α-N-Methylgranatanyl-                                                                     249                                                        methobromide                                                  9       OH      3α-N-Isopropylgranatanyl-                                                                  219-20                                                     methobromide                                                  10      OH      3α-(6,7-Dehydro)tropanyl-                                                                  207-8                                                      methobromide                                                  11      H       3α-(6,7-Dehydro)tropanyl-                                                                  214-5                                                      methobromide                                                  12      OH      3α-(6,7-Dehydro)-N-isopropyl-                                                              223                                                        nortropanyl-methobromide                                      13      H       3α-Nortropanyl-8,1'-                                                                       231-2                                                      pyrrolidinium-bromide                                         ______________________________________                                    

                  TABLE III                                                       ______________________________________                                        Compounds of formula                                                           ##STR12##                                                                    No.     R.sub.1 A                  M.p.  °C.!                          ______________________________________                                        1       H       3α-(6β,7β-Epoxy)-tropanyl-                                                       213-4                                                      methobromide                                                  2       H       3α-(6β,7β-Epoxy)-tropanyl-                                                       204-5                                                      propargochloride                                              3       H       3α-N-Ethyl-(6β,7β-Epoxy)-                                                        201                                                        nortropanyl-methobromide                                      4       H       3α-(6,7-Dehydro)tropanyl-                                                                  238-9                                                      methobromide                                                  5       H       3α-Tropanyl-methobromide                                                                   203-5                                      6       OH      3α-(6β,7β-Epoxy)tropanyl-                                     metho-methanesulphonate                                       ______________________________________                                    

                  TABLE IV                                                        ______________________________________                                        Compounds of formula                                                           ##STR13##                                                                    No.   R.sub.1 A                     M.p.  °C.!                         ______________________________________                                        1     H       3α-(6β,7β-Epoxy)-N-n-propyl                                                         213-4                                                   nortropanyl-methobromide                                        2     H       3α-(6β,7β-Epoxy)-N-isopropyl-                                                       242                                                     nortropanyl-methobromide                                        3     H       3α-(6β,7β-Epoxy)-N-ethyl-                                                           217                                                     nortropanyl-methobromide                                        4     H       3α-(6β,7β-Epoxy)tropanyl-                                                           139                                                     methobromide (with crystal ether)                               5     H       3α-(6β,7β-Epoxy)tropanyl-                                                           128-31                                                  ethobromide                                                     6     H       3α-Tropanyl-ethobromide                                                                       212-3                                     7     OH      3α-N-Isopropylnortropanyl-                                                                    229-32                                                  metho-methanesulphonate                                         8     H       3α-N-Isopropylnortropanyl-                                                                    184-5                                                   methobromide                                                    9     H       3α-(6,7-Dehydro)-N-isopropyl-                                                                 259                                                     nortropanyl-methobromide                                        10    H       3α-(6,7-Dehydro)-tropanyl-                                                                    237-8                                                   methobromide                                                    ______________________________________                                    

                  TABLE V                                                         ______________________________________                                        Compounds of formula                                                           ##STR14##                                                                    No.  R.sub.1 R.sub.2 W     A            M.p.  °C.!                     ______________________________________                                        1    OH      H       H     3α-(6β,7β-Epoxy)-                                                          223                                                              tropanyl-methobromide                              2    CH.sub.2 OH                                                                           H       H     3α-(6β,7β-Epoxy)-                                                          190                                                              tropanyl-ethobromide                               3    H       Cyclo-  H     3α-(6β,7β-Epoxy)-                                                          242                                                heptyl        tropanyl-methobromide                              4    H       Cyclo-  H     3α-(6β,7β-Epoxy)-                                                          215-6                                              heptyl        tropanyl-propobromide                              5    --C.sub.5 H.sub.8 --                                                                      H       3α-(6β,7β-Epoxy)-                                                          223-4                                                            tropanyl-methobromide                                6    CH.sub.2 OH                                                                           H       H     3α-(6β,7β-Epoxy)-N-                                                        194                                                              (β-fluorethyl)-nor-                                                      tropanyl-methobromide                              7    CH.sub.2 OH                                                                           H       H     3α-(6β,7β-Epoxy)-N-                                                        211                                                              (β-hydroxyethyl)-                                                        nortropanyl-                                                                  methobromide                                       8    OH      C.sub.6 H.sub.4                                                                       4-F   3α-Tropanyl-                                                                         220-1                                                            methobromide                                       9    --C.sub.5 H.sub.8 --                                                                      H       3α-Tropanyl-                                                                         287-9                                                            methobromide                                         10   --C.sub.5 H.sub.8 --                                                                      H       3α-N-Isopropyl-                                                                      263                                                              nortropanyl-                                                                  methobromide                                         11   --C.sub.6 H.sub.10 --                                                                     H       3α-N-Isopropyl-                                                                      261                                                              nortropanyl-                                                                  methobromide                                         12   OH      C.sub.6 H.sub.11                                                                      H     3α-(6,7-Dehydro)-                                                                    233-5                                                            tropanyl-methobromide                              13   H       C.sub.6 H.sub.11                                                                      3-CH.sub.3                                                                          3α-N-Isopropyl-                                                                      252-4                                                            nortropanyl-                                                                  methobromide                                       14   H       C.sub.5 H.sub.9                                                                       3-CH.sub.3                                                                          3α-Nortropanyl-                                                                      224-6                                                            8,1'-pyrrolidinium-                                                           bromide                                            ______________________________________                                    

                  TABLE VI                                                        ______________________________________                                        Compounds of formula                                                           ##STR15##                                                                    No.    A                   R.sub.1 M.p.  °C.!                          ______________________________________                                        1      3α-(6β,7β-Epoxy)-tropanyl-                                                        H       176                                               methobromide.H.sub.2 O                                                 2      3α-Tropanyl-methobromide                                                                    H                                                  3      3α-(6,7-Dehydro)-tropanyl-                                                                  OH                                                        methobromide                                                           4      3α-(N-β-Fluorethyl)-nortropanyl-                                                       H                                                         methobromide                                                           5      3α-Tropanyl-β-fluorethobromide                                                         OH                                                 6      3α-(N-Isopropyl)-granatanyl-                                                                H                                                         methobromide                                                           7      3α-(N-Isopropyl)-nortropanyl-                                                               H                                                         methobromide                                                           8      3α-(6β,7β-Epoxy)-N-isopropyl-                                                     OH                                                        nortropanyl-methobromide                                               9      3α-(6β,7β-Epoxy)-N-ethylnor-                                                      OH                                                        tropanyl-methobromide                                                  10     3α-(N-Ethyl)-nortropanyl-                                                                   OH                                                        methobromide                                                           11     3α-(N-Methyl)-granatanyl-                                                                   CH.sub.3                                                  methobromide                                                           ______________________________________                                    

                  TABLE VII                                                       ______________________________________                                        Compounds of formula                                                           ##STR16##                                                                    No.     A                 R.sub.1  M.p.  °C.!                          ______________________________________                                        1       3α-(6β,7β-Epoxy)-tropanyl-                                                      H                                                           methobromide                                                          2       3α-(6,7-Dehydro)-tropanyl-                                                                H                                                           methobromide                                                          3       3α-(6β,7β-Epoxy)-tropanyl-                                                      Methyl                                                      methobromide                                                          4       3α-(6,7-Dehydro)-tropanyl-                                                                Methyl                                                      methobromide                                                          5       3α-(6β,7β-Epoxy)-tropanyl-                                                      OH                                                          methobromide                                                          6       3α-(6,7-Dehydro)-tropanyl-                                                                OH                                                          methobromide                                                          ______________________________________                                    

                  TABLE VIII                                                      ______________________________________                                        Compounds of formula                                                           ##STR17##                                                                    No.   A                 R.sub.2    M.p.  °C.!                          ______________________________________                                        1     3α-(6β,7β-Epoxy)-tropanyl-                                                      Phenyl                                                      methobromide                                                            2     3α-(6,7-Dehydro)-tropanyl-                                                                Phenyl                                                      methobromide                                                            3     3α-(6β,7β-Epoxy)-tropanyl-                                                      Cyclopentyl                                                 methobromide                                                            4     3α-(6,7-Dehydro)-tropanyl-                                                                3-Thienyl                                                   methobromide                                                            5     3α-Tropanyl-methobromide                                                                  3-Thienyl                                             6     3α-(N-Methyl)-granatanyl-                                                                 3-Thienyl                                                   methobromide                                                            ______________________________________                                    

                  TABLE IX                                                        ______________________________________                                        Compounds of formula                                                           ##STR18##                                                                    No.   A                 R.sub.2    M.p.  °C.!                          ______________________________________                                        1     3α-(6β,7β-Epoxy)-tropanyl-                                                      Phenyl                                                      methobromide                                                            2     3α-(6,7-Dehydro)-tropanyl-                                                                Phenyl                                                      methobromide                                                            3     3α-(6β,7β-Epoxy)-tropanyl-                                                      Cyclopentyl                                                 methobromide                                                            4     3α-(6,7-Dehydro)-tropanyl-                                                                3-Thienyl                                                   methobromide                                                            5     3α-Tropanyl-methobromide                                                                  3-Thienyl                                             6     3α-(N-Methyl)-granatanyl-                                                                 3-Thienyl                                                   methobromide                                                            ______________________________________                                    

                  TABLE X                                                         ______________________________________                                        Compounds of formula                                                           ##STR19##                                                                    No.   A                 R.sub.1    M.p.  °C.!                          ______________________________________                                        1     3α-(6β,7β-Epoxy)-tropanyl-                                                      H                                                           methobromide                                                            2     3α-(6,7-Dehydro)-tropanyl-                                                                H                                                           methobromide                                                            3     3α-(6β,7β-Epoxy)-tropanyl-                                                      Methyl                                                      methobromide                                                            4     3α-(6,7-Dehydro)-tropanyl-                                                                Methyl                                                      methobromide                                                            5     3α-(6β,7β-Epoxy)-tropanyl-                                                      OH                                                          methobromide                                                            6     3α-(6,7-Dehydro)-tropanyl-                                                                OH                                                          methobromide                                                            ______________________________________                                    

                  TABLE XI                                                        ______________________________________                                        Compounds of formula                                                           ##STR20##                                                                    No.       A                   M.p.  °C.!                               ______________________________________                                        1         3α-(6β,7β-Epoxy)-tropanyl                                     methobromide                                                        2         3α-(6,7-Dehydro)-tropanyl-                                              methobromide                                                        3         3α-(6β,7β-Epoxy)-tropanyl-                                    ethobromide                                                         4         3α-(6,7-Dehydro)-tropanyl-                                              ethobromide                                                         5         3α-Tropanyl                                                             methobromide                                                        6         3α-(N-Methyl)-granatanyl-                                               methobromide                                                        ______________________________________                                    

                  TABLE XII                                                       ______________________________________                                        Compounds of formula                                                           ##STR21##                                                                    No.       A                   M.p.  °C.!                               ______________________________________                                        1         3α-(6β,7β-Epoxy)-tropanyl-                                    methobromide                                                        2         3α-(6,7-Dehydro)-tropanyl-                                              methobromide                                                        3         3α-(6β,7β-Epoxy)-tropanyl-                                    ethobromide                                                         4         3α-(6,7-Dehydro)-tropanyl-                                              ethobromide                                                         5         3α-Tropanyl                                                             methobromide                                                        6         3α-(N-Methyl)-granatanyl-                                               methobromide                                                        ______________________________________                                    

                  TABLE XIII                                                      ______________________________________                                        Compounds of formula                                                           ##STR22##                                                                    No.       A                   M.p.  °C.!                               ______________________________________                                        1         3α-(6β,7β-Epoxy)-tropanyl-                                    methobromide                                                        2         3β-(6,7-Dehydro)-tropanyl-                                               methobromide                                                        3         3α-(6β,7β-Epoxy)-tropanyl-                                    ethobromide                                                         4         3α-(6,7-Dehydro)-tropanyl-                                              ethobromide                                                         5         3α-Tropanyl                                                             methobromide                                                        6         3α-(N-Methyl)-granatanyl-                                               methobromide                                                        ______________________________________                                    

                  TABLE XIV                                                       ______________________________________                                        Quarternary compounds of formula                                               ##STR23##                                                                    No.  A                    R.sub.2   M.p.  °C.!                         ______________________________________                                         1   3α-(6β,7β-Epoxy)-tropanyl-                                                         2-Thienyl                                                methobromide                                                              2   3α-Tropanyl-methobromide                                                                     2-Thienyl                                            3   3α-(6,7-Dehydro)-tropanyl-                                                                   2-Thienyl                                                methobromide                                                              4   3α-(N-β-Fluorethyl)-nortropanyl-                                                        2-Thienyl                                                methobromide                                                              5   3α-Tropanyl-β-fluorethobromide                                                          2-Thienyl                                            6   3α-(N-Isopropyl)-granatanyl-                                                                 2-Thienyl                                                methobromide                                                              7   3α-(N-Isopropyl)-nortropanyl-                                                                2-Thienyl                                                methobromide                                                              8   3α-(6β,7β-Epoxy)-N-isopropyl-                                                      2-Thienyl                                                nortropanyl-methobromide                                                  9   3α-(6β,7β-Epoxy)-N-ethylnor-                                                       2-Thienyl                                                tropanyl-methobromide                                                    10   3α-(N-Ethyl)-nortropanyl-                                                                    2-Thienyl                                                methobromide                                                             11   3α-(N-Methyl)-granatanyl-                                                                    2-Thienyl                                                methobromide                                                             12   3α-(6β,7β-Epoxy)-N-β-fluoroethyl-                                             2-Thienyl                                                nortropanyl-methobromide                                                 13   3α-(6β,7β-Epoxy)-N-n-propyl-                                                       2-Thienyl                                                nortropanyl-methobromide                                                 14   3α-Tropanyl-β-hydroxyethobromide                                                        2-Thienyl                                           15   3α-(6β,7β-Epoxy)-tropanyl-                                                         Phenyl                                                   methobromide                                                             16   3α-Tropanyl-methobromide                                                                     Phenyl                                              17   3α-(N-β-Fluoroethyl)-                                                                   Phenyl                                                   nortropanyl-methobromide                                                 18   3α-(6,7-Dehydro)-tropanyl-                                                                   Phenyl                                                   methobromide                                                             19   3α-(N-Ethyl)-nortropanyl-                                                                    Phenyl                                                   methobromide                                                             20   3α-(N-Isopropyl)-nortropanyl-                                                                Phenyl                                                   methobromide                                                             21   3α-Tropanyl-ethobromide                                                                      Phenyl                                              22   3α-(N-Ethyl)-nortropanyl-                                                                    Phenyl                                                   ethobromide                                                              23   3α-(6β,7β-Epoxy)-tropanyl-                                                         Phenyl                                                   ethobromide                                                              24   3α-Tropanyl-β-fluorthobromide                                                           Phenyl                                              25   3α-Tropanyl-methobromide                                                                     Cyclohexyl                                          26   3α-(N-β-Fluorethyl)-nortropanyl-                                                        Cyclohexyl                                               methobromide                                                             27   3α-Tropanyl-β-fluorethobromide                                                          Cyclohexyl                                          28   3α-Tropanyl-methobromide                                                                     Cyclopentyl                                         29   3α-Tropanyl-ethobromide                                                                      Cyclopentyl                                         30   3α-(N-Ethyl)-nortropanyl-                                                                    Cyclopentyl                                              methobromide                                                             31   3α-(N-Isopropyl)-nortropanyl-                                                                Cyclopentyl                                              methobromide                                                             32   3α-Tropanyl-β-fluorethobromide                                                          Cyclopentyl                                         33   3α-(N-β-Fluorethyl)-nortropanyl-                                                        Cyclopentyl                                              methobromide                                                             34   3α(6,7-Dehydro)-tropanyl-                                                                    2-Thienyl                                                metho-methanesulphonate                                                  35   3β-(6β,7β-Epoxy)-tropanyl-                                                          2-Thienyl                                                methobromide                                                             36   3β-Tropanyl-methobromide                                                                      2-Thienyl                                           37   3β-(6,7-Dehydro)-tropanyl-                                                                    2-Thienyl                                                methobromide                                                             38   3α(6,7-Dehydro)-tropanyl-                                                                    3-Thienyl                                                methobromide                                                             39   3α-(6β,7β-Epoxy)-tropanyl-                                                         3-Thienyl                                                methobromide                                                             40   (+)-Enantiomer of No. 1                                                  41   (-)-Enantiomer of No. 1                                                  42   3α-(6β,7β-Epoxy)tropanyl-                                                          2-Furyl                                                  methobromide                                                             43   3α-(6,7-Dehydro)-tropanyl-                                                                   2-Furyl                                                  methobromide                                                             44   3α-Tropanyl-methobromide                                                                     2-Furyl                                             45   3α-(6β,7β-Epoxy)-tropanyl                                                          2-Pyridyl                                                methobromide                                                             46   3α-(6,7-Dehydro)-tropanyl                                                                    2-Pyridyl                                                methobromide                                                             47   3α-Tropanyl-methobromide                                                                     2-Pyridyl                                           48   3α-Tropanyl-methobromide                                                                     3-Thienyl                                           49   3α-(6,7-Dehydro)-tropanyl                                                                    Cyclopentyl                                              methobromide                                                             50   3α-(6β,7β-Epoxy)-tropanyl                                                          Cyclohexyl                                               methobromide                                                             51   3α-(6,7-Dehydro)-tropanyl                                                                    Cyclohexyl                                               methobromide                                                             52   3α-(6β,7β-Epoxy)-tropanyl                                                          Cyclopentyl                                              methobromide                                                             ______________________________________                                    

                  TABLE XV                                                        ______________________________________                                        Compounds of formula                                                           ##STR24##                                                                                                            M.p                                   No.  A                R.sub.2    R.sub.a                                                                               °C.!                          ______________________________________                                        1    3α-(6β,7β-Epoxy)-tropanyl-                                                     2-Thienyl  5-Methyl                                          methobromide                                                             2    3α-(6,7-Dehydro)-tropanyl-                                                               2-Thienyl  5-Methyl                                          methobromide                                                             3    3α-Tropanyl-methobromide                                                                 2-Thienyl  5-Methyl                                     4    3α-(6β,7β-Epoxy)-tropanyl-                                                     2-(5-Methyl)-                                                                            5-Methyl                                          methobromide     thienyl                                                 5    3α-(6,7-Dehydro)-tropanyl-                                                               2-(5-Methyl)-                                                                            5-Methyl                                          methobromide     thienyl                                                 6    3α-Tropanyl-methobromide                                                                 2-(5-Methyl)-                                                                            5-Methyl                                                           thienyl                                                 7    3α-(6β,7β-Epoxy)-tropanyl-                                                     2-Thienyl  5-Fluoro                                          methobromide                                                             8    3α-(6,7-Dehydro)-tropanyl-                                                               2-Thienyl  5-Fluoro                                          methobromide                                                             9    3α-Tropanyl-methobromide                                                                 2-Thienyl  5-Fluoro                                     10   3α-(6β,7β-Epoxy)-tropanyl-                                                     2-(5-Fluoro)-                                                                            5-Fluoro                                          methobromide     thienyl                                                 11   3α-(6,7-Dehydro)-tropanyl-                                                               2-(5-Fluoro)-                                                                            5-Fluoro                                          methobromide     thienyl                                                 12   3α-Tropanyl-methobromide                                                                 2-(5-Fluoro)-                                                                            5-Fluoro                                                           thienyl                                                 ______________________________________                                    

                  TABLE XVI                                                       ______________________________________                                        Compounds of formula                                                           ##STR25##                                                                    No.    A                 R.sub.2   M.p.  °C.!                          ______________________________________                                        1      3α-(6β,7β-Epoxy)-tropanyl                                                       Phenyl                                                      methobromide                                                           2      3α-(6,7-Dehydro)-tropanyl                                                                 Phenyl                                                      methobromide                                                           3      3α-(6β,7β-Epoxy)-tropanyl                                                       3-Thienyl                                                   methobromide                                                           4      3α-(6,7-Dehydro)-tropanyl                                                                 3-Thienyl                                                   methobromide                                                           5      3α-Tropanyl 3-Thienyl                                                   methobromide                                                           6      3α-(N-Methyl)-granatanyl                                                                  3-Thienyl                                                   methobromide                                                           ______________________________________                                    

                  TABLE XVII                                                      ______________________________________                                        Compounds of formula                                                           ##STR26##                                                                    No.      A                    M.p. °C.!                                ______________________________________                                         1       3α-(6β,7β-Epoxy)-tropanyl-                                    methobromide                                                          2       3α-Tropanyl-methobromide                                        3       3α-(6,7-Dehydro)-tropanyl-                                              methobromide                                                          4       3α-(N-β-Fluorethyl)-nortropanyl-                                   methobromide                                                          5       3α-Tropanyl-β-fluorethobromide                             6       3α-(N-Isopropyl)-granatanyl-                                            methobromide                                                          7       3α-(N-Isopropyl)-nortropanyl-                                           methobromide                                                          8       3α-(6β,7β-Epoxy)-N-isopropyl-                                 nortropanyl-methobromide                                              9       3α-(6β,7β-Epoxy)-N-ethylnor-                                  tropanyl-methobromide                                                10       3α-(N-Ethyl)-nortropanyl-                                               methobromide                                                         11       3α-(N-Methyl)-granatanyl-                                               methobromide                                                         12       3α-(6β,7β-Epoxy)-N-β-fluoroethyl-                        nortropanyl-methobromide                                             13       3α-(6β,7β-Epoxy)-N-n-propyl-                                  nortropanyl-methobromide                                             14       3α-Tropanyl-β-hydroxyethobromide                          15       3α(6,7-Dehydro)-tropanyl-                                               metho-methanesulphonate                                              16       3β-(6β,7β-Epoxy)-tropanyl-                                     methobromide                                                         17       3β-Tropanyl-methobromide                                        18       3β-(6,7-Dehydro)-tropanyl-                                               methobromide                                                         ______________________________________                                    

                  TABLE XVIII                                                     ______________________________________                                        Compounds of formula                                                           ##STR27##                                                                    No.     A                 R.sub.1  M.p.  °C.!                          ______________________________________                                        1       3α-(6β,7β-Epoxy)-tropanyl                                                       OH                                                          methobromide                                                          2       3α-(6,7-Dehydro)-tropanyl                                                                 OH                                                          methobromide                                                          3       3α-(6β,7β-Epoxy)-tropanyl                                                       Methyl                                                      methobromide                                                          4       3α-(6,7-Dehydro)-tropanyl                                                                 Methyl                                                      methobromide                                                          5       3α-Tropanyl H                                                           methobromide                                                          6       3α-(N-Ethyl)-nortropanyl                                                                  H                                                           methobromide                                                          ______________________________________                                    

                  TABLE A                                                         ______________________________________                                        Compounds of formuia                                                           ##STR28##                                                                                                          Mp.  °C.!                                                              Hydro-                                  No.  A                R.sub.2   Base  chloride                                ______________________________________                                         1   3α-(6β,7β-Epoxy)-tropanyl                                                      2-Thienyl 149-50                                                                              238-41                                   2   3α-Tropanyl                                                                              2-Thienyl 167-8 253                                      3   3α-(6,7-Dehydro)-tropanyl                                                                2-Thienyl 164-5                                          4   3α-(N-β-Fluorethyl)-                                                                2-Thienyl       236                                          nortropanyl                                                               5   3α-(N-Isopropyl)-                                                                        2-Thienyl       232                                          granatanyl                                                                6   3α-(N-Isopropyl)-                                                                        2-Thienyl       250                                          nortropanyl                                                               7   3α-(6β,7β-Epoxy)-N-iso-                                                        2-Thienyl       206                                          propylnortropanyl                                                         8   3α-(6β,7β-Epoxy)-N-ethyl-                                                      2-Thienyl       212-3                                        nortropanyl                                                               9   3α-(N-Ethyl)-nortropanyl                                                                 2-Thienyl       256-7                                   10   3α-(N-Methyl)-granatanyl                                                                 2-Thienyl       241                                     11   3α-(6β,7β-Epoxy)-N-β-                                                     2-Thienyl       188-90                                       fluorethylnortropanyl                                                    12   3α-(6β,7β-Epoxy)-N-n-                                                          2-Thienyl 104-6                                              propylnortropanyl                                                        13   3α(6β,7β-Epoxy)-N-n-                                                           2-Thienyl       225-7                                        butylnortropanyl                                                         14   3α-(6β,7β-Epoxy)-tropanyl                                                      Phenyl          246-7                                   15   3α-Tropanyl                                                                              Phenyl          243-4                                   16   3α-(N-β-Fluoroethyl)-                                                               Phenyl          219-20                                       nortropanyl                                                              17   3α-(6,7-Dehydro)-tropanyl                                                                Phenyl    181-3                                         18   3α-(N-Ethyl)-nortropanyl                                                                 Phenyl          231-2                                   19   3α-(N-Isopropyl)-                                                                        Phenyl          246-7                                        nortropanyl                                                              20   3α-Tropanyl                                                                              Cyclohexyl      260                                     21   3α-(N-β-Fluoroethyl)-                                                               Cyclohexyl      203-4                                        nortropanyl                                                              22   3α-(6β,7β-Epoxy)-tropanyl                                                      Cyclopentyl     237                                     23   3α-Tropanyl                                                                              Cyclopentyl     260                                     24   3α-(N-β-Fluoroethyl)-                                                               Cyclopentyl     182-3                                        nortropanyl                                                              25   3α-(N-Ethyl)-nortropanyl                                                                 Cyclopentyl     227-8                                   26   3α-(N-Isopropyl)-                                                                        Cyclopentyl     174-5                                        nortropanyl                                                              27   3β-(6β,7β-Epoxy)-tropanyl                                                       2-Thienyl       240-2                                   28   3β-Tropanyl 2-Thienyl       217-9                                   29   3β-(6,7-Dehydro)-tropanyl                                                                 2-Thienyl       233-5                                   30   3α-(6,7-Dehydro)-tropanyl                                                                3-Thienyl       247-8                                   31   3α-(6β,7β-Epoxy)-tropanyl                                                      3-Thienyl       242-3                                   32   3α-(6β,7β-Epoxy)-tropanyl                                                      2-Furyl                                                 33   3α-(6,7-Dehydro)-tropanyl                                                                2-Furyl                                                 34   3α-Tropanyl                                                                              2-Furyl                                                 35   3α-Tropanyl                                                                              2-Pyridyl                                               36   3α-(6β,7β-Epoxy)-tropanyl                                                      2-Pyridyl                                               37   3α-(6,7-Dehydro)-tropanyl                                                                2-Pyridyl                                               38   3α-Tropanyl                                                                              3-Thienyl                                               39   3α-(6,7-Dehydro)-tropanyl                                                                Cyclopentyl                                             40   3α-(6β,7β-Epoxy)-tropanyl                                                      Cyclohexyl                                              41   3α-(6,7-Dehydro)-tropanyl                                                                Cyclohexyl                                              ______________________________________                                         Note: all hydrochlorides melt with decomposition.                        

We claim:
 1. A compound of formula ##STR29## wherein R is an optionallyhalo- or hydroxy-substituted C₁₋₄ -alkyl group;R' is a C₁₋₄ -alkylgroup; or R and R' together form a C₄₋₆ -alkylene group; X⁻ is ananion;and R₁ is H, OH, CH₂ OH, C₁₋₄ -alkyl or C₁₋₄ -alkoxy.
 2. Thecompound according to claim 1, wherein X⁻ is bromide.
 3. The compoundaccording to claim 1, wherein R₁ is OH, CH₃ or CH₂ OH.
 4. The compoundaccording to claim 1, wherein R is methyl and R' is methyl, ethyl,n-propyl or i-propyl.
 5. A pharmaceutical composition comprising acompound according to any one of claims 1-4 and a pharmaceuticallyacceptable excipient or carrier.
 6. A method for treating a diseasewhich is responsive to an anti-cholinergic agent in a warm-bloodedanimal, comprising the step of administering to said animal atherapeutically effective amount of the pharmaceutical compositionaccording to claim
 5. 7. The method according to claims 6, wherein saidpharmaceutical composition is administered by inhalation.
 8. The methodaccording to claim 6, wherein said pharmaceutical composition isadministered intravenously or orally.
 9. A method for treating arespiratory tract disease in a warm-blooded animal, comprising the stepof administering to said animal a therapeutically effective amount ofthe pharmaceutical composition according to claim
 5. 10. The methodaccording to claim 9, wherein said pharmaceutical composition isadministered by inhalation.
 11. The method according to claim 9, whereinsaid pharmaceutical composition is administered Intravenously or orally.12. A method for treating sinus bradycardia in a warm-blooded animal,comprising the step of administering to said animal a therapeuticallyeffective amount of the pharmaceutical composition according to claim 5.13. The method according to claim 12, wherein said pharmaceuticalcomposition is administered by inhalation.
 14. The method according toclaim 12, wherein said pharmaceutical composition is administeredintravenously or orally.